Antispasmodics Overview Quiz

Spasmolytics are drugs that suppress or reduce muscle contractions.
They are used as antimotility agents which reduce contractions and movement in the gastrointestinal tract.
Spasmolytics can be grouped into three categories: antimuscarinics (M3 receptor antagonists), opioids, and sympathomimetics.
Antimuscarinic examples include hyoscine (scopolamine), propantheline, and dicycloverine. Antimuscarinics may cause dry mouth, constipation, and mydriasis (dilated pupils).
Loperamide is an opioid antispasmodic that selectively targets the gastrointestinal tract and does not cross the blood-brain barrier.
Loperamide undergoes enterohepatic recycling and also has anti-secretory effects against cholera and E. coli toxin.
Diphenoxylate lacks morphine's central nervous system activity but can cross the blood-brain barrier at high doses.
Diphenoxylate is combined with atropine to reduce the dose of diphenoxylate.
Diphenoxylate is administered orally and has an active metabolite, Diphenoxin, that contributes to its long half-life. Side effects include megacolon, dry mouth, and blurred vision.
Clonidine is a sympathomimetic that acts as an α2 receptor agonist.
Clonidine inhibits gastrointestinal motility by binding to α2 receptors on the GI tract.

Emetics are agents that induce vomiting.
They are sometimes used to remove ingested substances that are harmful or poisonous.
Clinical use of emetics is diminishing due to potential adverse effects.

Apomorphine is a centrally acting emetic that is administered subcutaneously or intravenously.
Apomorphine causes vomiting accompanied by sedation.
It is a non-selective dopamine receptor agonist.
Side effects include hypotension, syncope, tremors, and restlessness.

Hypertonic sodium chloride is administered orally and acts peripherally by withdrawing fluid from stomach cells, leading to irritation and emesis.

Ipecacuanha is derived from the dry root of Cephalis ipecacuanha and contains emetine as the active constituent.
Emetine works both centrally through the chemoreceptor trigger zone and peripherally by irritating the gastric mucosa to induce vomiting.
Ipecacuanha is usually formulated as "syrup of ipecac" for administration.

Examples include ondansetron, dolasetron, and granisetron.
Ondansetron is administered orally, intravenously, and intramuscularly.
It is well absorbed from the gastrointestinal tract and extensively metabolized in the liver.
Hepatic dysfunction reduces the plasma clearance of these drugs.
The metabolism of granisetron is affected by ketoconazole (CYP3A inhibition by ketoconazole).
Ondansetron also binds to serotonin 5HT3 receptors in the gastrointestinal tract, providing an additional mechanism against emesis.
Palonosetron is a second-generation serotonin 5HT3 antagonist with better receptor affinity and a longer half-life (>30 hours).
Ondansetron is well tolerated with main side effects including diarrhea, headache, and lightheadedness.
They are effective for chemotherapy-induced and postoperative emesis.

Examples include chlorpromazine, prochlorperazine, and metoclopramide.
They antagonize dopamine receptors in the chemoreceptor trigger zone (CTZ).
They also possess anticholinergic and antihistaminergic actions that enhance their antiemetic effects.
They are beneficial in treating motion sickness.

Examples include diphenhydramine, cyclizine, promethazine, and cinnarizine.
They are primarily used for emesis associated with motion sickness and vertigo caused by labyrinthine disorders.
They also possess anticholinergic activity.
Antihistamines antagonize histamine H1 receptors on the vestibular afferents.

Example is scopolamine.
Scopolamine acts as an alternative to antihistamines for preventing motion sickness.
It binds to muscarinic M1 receptors in the chemoreceptor trigger zone and the gastrointestinal tract to suppress emesis.
It may cause anticholinergic side effects.

Examples include nabilone and dronabinol.
Δ9-tetrahydrocannabinol (THC), a natural component of cannabis, has antiemetic actions.
Synthetic cannabinoids such as nabilone and dronabinol stimulate CB1 receptors around the vomiting center.
Cannabinoids are psychoactive and highly lipid-soluble compounds that are rapidly absorbed.
They undergo extensive first-pass metabolism and have limited systemic bioavailability.
They are highly plasma protein bound and have a large volume of distribution.
They are used in combination with other anti-emetics for chemotherapy-induced emesis.
Adverse effects include central nervous system symptoms, prominent sympathomimetic effects ( palpitations, tachycardia, conjunctival redness), euphoria, anxiety, insomnia, and restlessness.

Examples include aprepitant, fosaprepitant, and rolapitant.
Aprepitant is a neurokinin receptor antagonist that blocks the actions of substance P and has a delayed emetic action. It is typically used in combination therapy for delayed emesis.
Fosaprepitant is a prodrug given intravenously.
Fosaprepitant is extensively plasma protein bound and metabolized via CYP3A4 in the liver.
Side effects include diarrhea, fatigue, and hiccups.
They are used in combination with other antiemetics for chemotherapy-induced emesis.

These agents are not very effective anti-emetics on their own and are often used in combination with other anti-emetics.
Examples include benzodiazepines and corticosteroids.
Benzodiazepines, such as diazepam, lorazepam, and alprazolam, are helpful in anticipatory emesis due to their sedative and antianxiety actions.
Corticosteroids (e.g., dexamethasone, prednisolone, methylprednisolone) block the production of prostaglandins that trigger the emetogenic signal.

It is contraindicated to use emetics on patients who are unconscious, have solvent or volatile hydrocarbon poisoning, or who have corrosive alkaline poisoning.